Our overall objective is to find means of altering the expression of the transformed genome of mammary epithelial cells be they preneoplastic or neoplastic. A definite preneoplastic stage has been demonstrated in the murine model system that we are utilizing for most of our studies. To establish indicators of changes in genomic expression, we have continued to characterize this mammary system metabolically and biochemically. For example, identification of individual isoenzyme patterns (glucose-6-phosphate dehydrogenase) and fatty acid composition analysis in normal, preneoplastic and neoplastic tissues indicates specific differences exist between tissues. These differences may be used to identify cellular transformations. Studies directly aimed at influencing genomic expression are being carried out at three levels of tissue complexity: isolated cells, organ or tissue culture, and the intact animal. Thus far, hormonal and nutritional manipulations have been employed to alter the phenotype of the preneoplastic and neoplastic cells. For instance, studies with intact mice have demonstrated that dietry linoleate (1 percent) significantly increases the growth rate of mammary adenocarcinomas. Drugs known to inhibit prostaglandin synthesis are effective in inhibiting the growth promoting effect of dietary linoleate. BIBLIOGRAPHIC REFERENCES: "Fatty Acid Synthase from Lactating Rat Mammary Gland," Stuart Smith and S. Abraham in Methods in Enzymology, Volume XXXV Lipids, Part B, pp. 65-74, 1975. Edited by John M. Lowenstein, Academic Press, Inc., New York. "Effects of Pharmacologic Agents on Hepatic Biosynthesis of Fatty Acids and Cholesterol," Stuart Smith and S. Abraham in International Encyclopedia of Pharmacology and Therapeutics, Section 24, Chapter 4, pp. 69-124, 1975. Edited by E.J. Masoro, Pergamon Press, Ltd., Oxford, England.